The gastrointestinal (GI) tract has several regions sharply demarcated by local pH ranging from 5.5 to 8.2. The distal ileum further uniquely contains a region where the usual pH is between 7.3 and 8.2. Notably, this area is relatively devoid of degradation pathways for antigens such as vaccine constructs, yet far more sensitive to their presence.
Many antigens are degraded by the acid and proteolytic conditions of the stomach and anterior GI tract, conditions which make oral vaccination impractical to nearly impossible from a technical point of view. Thus, the distal ileum and the area of the ileal brake, which is optimal for a controlling sensor for nutritional balance, also uniquely contains both the optimum pH conditions for vaccination (stability of antigenic substance) and contains numerous specialized sensing cells (such as Peyer's Patches), that help to define the immune system response to the foreign invader pathogens and in some cases, tumors.
The appendix, by way of example in the art, is a specialized sensor located distal to the ileum in the right colon. It contains lymphoid tissue and has long been thought to be involved in the activation of the B cell response to antigens of all types. Because of relative inaccessibility to formulations, neither the distal ileum nor the appendix has been used as a target site for oral vaccination, and although the use of these areas of lymphoid tissue are logical targets for vaccine delivery, it has been thought impossible to achieve.
Accordingly, the need exists for oral vaccines that enable effective delivery of a wide variety of antigens in the region of the distal ileum and ileal brake, thereby avoiding antigen degradation encountered with known orally-dosed vaccines.